The Binding Mode of a Tau Peptide with Tubulin
The Binding Mode of a Tau Peptide with Tubulin
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DOI：
10.1002/anie.201712089
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发表时间：
2018-03-12
影响因子：
16.6
通讯作者：
Zweckstetter, Markus
中科院分区：
文献类型：
--
作者：
Kadavath, Harindranath;Fontela, Yunior Cabrales;Zweckstetter, Markus
微管相关蛋白Tau促进微管蛋白的聚合，调节微管的功能。由于Tau-微管蛋白相互作用的动态性质，这种复合体的结构基础在很大程度上仍然难以捉摸。通过使用针对配体-受体相互作用进行优化的核磁共振方法，结合定点突变，我们证明了Tau的四个微管结合重复序列下游的侧翼结构域竞争性地与微管蛋白表面的一个位点结合。结合过程复杂，涉及不同相互作用区的部分偶联，并受Y394和S396的磷酸化调控。这项研究加强了Tau磷酸化和微管蛋白结合之间密切关系的假设，并强调了INPHARMA核磁共振方法在表征来自内在无序蛋白质的多肽与其分子伴侣相互作用方面的能力。
The microtubule-associated protein Tau promotes the polymerization of tubulin and modulates the function of microtubules. As a consequence of the dynamic nature of the Tau-tubulin interaction, the structural basis of this complex has remained largely elusive. By using NMR methods optimized for ligand-receptor interactions in combination with site-directed mutagenesis we demonstrate that the flanking domain downstream of the four microtubule-binding repeats of Tau binds competitively to a site on the -tubulin surface. The binding process is complex, involves partial coupling of different interacting regions, and is modulated by phosphorylation at Y394 and S396. This study strengthens the hypothesis of an intimate relationship between Tau phosphorylation and tubulin binding and highlights the power of the INPHARMA NMR method to characterize the interaction of peptides derived from intrinsically disordered proteins with their molecular partners.